The presence and severity of chest pain in patients does not always correlate with the presence and magnitude of myocardial ischemia. To test the hypothesis that increased myocardial sensitivity may contribute to cardiac pain, 3 groups of patients with chest pain, and one group with heart disease but without a clinical history of chest pain were studied during diagnostic cardiac catheterization. Intracardiac visceral sensitivity was assessed by probing the right atrium and right ventricle with a pacing wire, and pacing from the right atrial appendage and right ventricular apex at 5 beats faster than resting heart rate, and at pacing stimulus intensities ranging from 1 to 10 milliamps. These manipulations produced chest pain typical of that previously experienced in 29 of 36 (81%) patients with chest pain and angiographically normal coronary arteries, and 15 of 33 (46%) symptomatic patients with hypertrophic cardiomyopathy. In contrast, only 2 of 33 (6%) symptomatic patients with coronary artery disease experienced their typical chest pain with these sensitivity tests (p>0.001). None of 10 patients with valvular heart disease but without a chest pain syndrome experienced any sensation with these tests. Cutaneous pain threshold testing demonstrated the patients with chest pain and angiographically normal coronary arteries had a higher pain threshold to thermal stimulation compared to patients who had coronary artery disease or hypertrophic cardiomyopathy. No relation existed between cardiac sensitivity and cutaneous sensitivity testing. Thus, patients with chest pain syndromes despite angiographically normal coronary arteries may have abnormal cardiac sensitivity to a variety of stimuli which may be of causal importance to their chest pain syndrome or contribute to their perception of ischemia-mediated pain.